Biomolecular modeling and simulation lies at the heart of physically inspired methods for understanding molecular biology and structural biochemistry. Empirical force fields have been approaching a generational transition over the past several years, moving away from well- established, well-tuned but intrinsically limited fixed point charge models towards more intricate and accurate polarizable potentials. This research proposes to extend the polarizable AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Applications) force field to nucleic acid systems. Together with the current AMOEBA protein parameterization, this will provide a consistently derived model for the two major biopolymer classes. The required electrostatic parameter for nucleic acids will be derived from high-level quantum mechanical electronic structure calculations. In order to use AMOEBA for DNA and RNA systems, several new energy functions will be needed to treat currently neglected effects, such as charge transfer, penetration of electron densities, and damping of dispersion at short distance ranges. The resulting next-generation of the AMOEBA force field promises to significantly improve the accuracy of short-range interactions over other currently available force fields. Nucleic acids, and their interaction with ions, small molecules and proteins, underlie much of human biochemistry, physiology and genetics. This research will calibrate the AMOEBA nucleic acid potentials on a series of structural motifs, against drug-RNA binding data, and with respect to interactions with ions. The validated force field will then open future opportunities for modeling of transcription factor interactions with DNA, detailed binding calculations for aminoglycoside antibiotics with the ribosome, and similar problems not approachable at present with polarizable force fields.